Proteins which exert a toxic effect on cells were found to be secreted, in response to stimulation, by mononuclear cells of various kinds. T-cells, or probably both the helper and the suppressor subsets can respond to antigens recognized by them, as well as to mitogenic lectins, by secreting such cytotoxic proteins (Granger, G. A. and Kolb, W. P., J. Imminol. 101, 111-120 (1968); Ruddle, N. H. and Waksman, B. H. J. Exp. Med. 128, 1267-1275 (1968); Eardley, D. D., Shen, F. W., Gershon, R. K. and Ruddle, N. H., J. Immunol. 124, 1199-1202 (1980)).
Monocytes and macrophages produce cytotoxic proteins in response to certain bacterial toxins (reviewed by Ruff, M. R. and G. E. Gifford in Lymphotoxins, E. Pick and M. Landy editors, Academic Press, Inc. New York, 235-272, (1981)). Natural killer cells secret cytotoxic proteins upon incubation with appropriate target cells (Wright, S. C. and Bonavia, B., J. Immunol. 129, 433-439, (1982)) while cells of certain continuous B lymphocyte lines were found to produce spontaneously cytotoxic proteins (Rosenau, W., Stites, D. and Jemtrud S., Cell. Immunol. 43, 235-244, (1979)). Proteins produced in lymphocyte cultures are usually referred to as "lymphotoxins", while the term "tumor necrosis factor" is often used for cytotoxic proteins produced in cultures of monocytes or of macrophages. Evidence has been presented that such cytotoxic proteins can selectively destroy tumor cells (Rundel, J. O. and Evans, C. H., Immunophormacol, 3, 9-18, (1981). So far, only a single protein of this type, produced spontaneously by cells of a B lymphocyte line has been characterized in some detail. It was purified to homogeneity and its molecular weight was estimated to be about 20,000 daltons (Aggarwal, B. B., Moffat, B. and Harkins, R. N., J. Biol. Chem. 259, 686-691 (1984)).